This unblinded, voluntary, open-label toxicity trial is assessing combination therapy of zidovudine plus lamivudine and, when indicated, indinavir as agents for postexposure chemoprophylaxis for health care workers (HCWs) sustaining occupational exposure to HIV. Indinavir may be added when the exposure is especially severe or drug-resistant HIV is suspected. This trial is a recent amendment to the protocol, which previously assessed the toxicity of zidovudine or zidovudine plus didanosine. The secondary purposes of this study are (1) to assess the effect of combination chemoprophylaxis on the temporal sequence of the appearance of markers of HIV infection should it occur in an HCW taking chemoprophylaxis and (2) to describe the epidemiology of exposures to HIV for which combination chemoprophylaxis is elected in institutions participating in this study. Zidovudine, lamivudine, and, if indicated, indinavir, are initiated as soon as possible for exposed HCWs, but not longer than 72 hours after exposure. Zidovudine dosage is 200 mg three times a day for 28 days. Lamivudine dose is 150 mg twice a day for 28 days. If indicated, indinavir can be added as a third agent at any time up to 72 hours after the first dose of zidovudine or lamivudine. The indinavir dose is 800 mg three times a day, and the total duration of prophylaxis remains at 28 days. Exposed HCWs are followed for a minimum of 12 months. After the baseline enrollment visit, followup visits occur at 2, 4, and 6 weeks and 3, 6, and 12 months. Individuals are assessed for drug toxicity as well as for early signs of HIV infection. Over 225 HCWs who have elected to take zidovudine have, in general, tolerated the drug well. Subjective toxicities occur in most HCWs; nonetheless, symptomatology has not correlated at all were objective hematologic toxicities. No investigator has discontinued any course of zidovudine because of laboratory toxicity in an HCW. Since June 1995 nine HCWs elected to take the zidovudine and didanosine combination therapy. Seven discontinued prophylaxis early because of subjective symptomatology. Again, the symptomatology was not correlated with objective hematologic toxicities. The new three-drug regimen was implemented July 1, 1996, and currently has one HCW enrolled.